Fig. 6

A signaling diagram illustrating the mediation role of fibronectin in activin A-increased human EVT migration, acquisition of endothelial-like phenotype and decidual vascularization at maternal-fetal interface. Activin A binds to the extracellular ligand-binding domain on trophoblast cells, and then, activin type I receptor (ActRI, ALK4) is recruited and phosphorylated. Phosphorylation of ALK4 leads to recruitment and phosphorylation of SMAD2/3, which forms a heterotrimeric SMAD complex with SMAD4. The trimeric SMAD complexes translocate from the cytoplasm to the nucleus and serve as transcription factors to modulate the expression of fibronectin. Fibronectin secreted and synthesized by EVTs is freely available in the microenvironment of the maternal-fetal interface and participates in activin A-promoted trophoblast migration and acquisition of endothelial-like phenotype, thus playing an important role in decidual vascularization and pregnancy maintenance. Created with BioRender.com